This proposal is concerned with two closely related problems: The mechanism of reverse transcription in vitro using the AMV enzyme and the structure of AMV RNA. We plan to investigate the mechanism by studying the kinetics of DNA synthesis, which we have already shown to be cooperative. Since the cooperativeness is a function of the AMV RNA concentration we deduce that the enzyme forms dimers or oligomers on the template. These studies will be extended to the separated subunits of the enzyme to determine whether this aggregation is between like or unlike subunits. We propose to determine the extent of copying of the viral RNA template in individual particles by autoradiography of disrupted virions, viral cores and 70S RNA molecules, to determine whether a few members of any of these classes may exhibit a much greater amount of synthesis than the average, which might constitute total transcription of the essential viral information. We will also look in virions for possible cofactors which will improve the quality and extent of reverse transcription. We will continue the fluorescence measurements we are using to determine the secondary structure of AMV RNA and will apply the method to a study of the structural changes that occur as a result of DNA synthesis.